1. Field of the Invention
The present invention relates to a method of detecting sentinel lymph nodes, into which tumor cells first enter from the primary nidus of a tumor, and a system therefor.
2. Description of the Related Art
In recent years, the rate of early detection of cancer has been on the rise, and early surgical removal of cancerous growths is frequently performed. Generally, the objective of early surgical removal of cancerous growths is the complete arresting of the disease, and frequently, in addition to the diseased tissue, a plurality of lymph nodes in the area surrounding the diseased tissue, from which there is a suspected danger of transferal of the disease, are also removed. In addition, after removal of the lymph nodes an examination to determine the cause of the disease and whether or not the disease has been transferred thereto is conducted thereon, and the course of post-surgical treatment is determined.
Due to the fact that it is not known whether or not the disease has been transferred to the lymph nodes during performance the surgical removal thereof, a plurality of lymph nodes in the surrounding vicinity of the diseased tissue is removed, and the burden on the patient is therefore great. Further, in the early stages of breast cancer, for example, the rate of transfer of the disease to lymph nodes is 20 percent, for the 80 percent of the patients in whom the disease has not been transferred to the lymph nodes, the removal thereof is unnecessary.
In recent years, there has been a movement to obtain both the complete arresting of cancer attained through surgical removal of the cancerous tissue while preserving the QOL (Quality of Life) of the patient. To this end, one surgical method that has received much attention, which is aimed at preventing unnecessary removal of lymph nodes, is sentinel node navigation surgery. Hereinafter, a simple explanation of sentinel node navigation surgery will be given.
For cases in which cancer has been transferred to lymph nodes, it has recently become clear, in light of recent research, that it is not transferred randomly, but is transferred through the lymph system to the lymph nodes according to a set pattern. The first lymph node into which cancer cells enter from the primary nidus of a cancer is called a sentinel lymph node. It is believed that for cases in which cancer has been transferred to the lymph nodes, the cancer has definitely been transferred to a sentinel lymph node.
Accordingly, by finding and excising the sentinel lymph node in a cancer removal surgery performed in the early stages of the disease and performing a biopsy on the excised sentinel lymph node, and expediently diagnosing the cause of the disease, it can be determined whether or not the cancer has been transferred to the lymph nodes.
For cases in which the cancer is found to not have been transferred to the lymph nodes, it is unnecessary to remove the remaining lymph nodes. For cases in which the cancer is found to have been transferred to the lymph nodes, depending upon the conditions, a plurality of lymph nodes are surgically removed from the vicinity surrounding the diseased tissue.
By performing sentinel node navigation surgery, it becomes unnecessary to remove lymph nodes of patients for whom it has been determined that cancer has not been transferred to their lymph nodes, and the burden on such patients is reduced. Moreover, this type of surgery is not limited to breast cancer, but can be employed in conjunction with open gastrointestinal tract surgery or procedures utilizing a laparoscope.
There is a strong demand for a method of accurately and easily detecting the sentinel lymph node when performing sentinel node navigation surgery. One conventional method of detecting the lymph node is the colorant method, employing a blue colorant. According to this method, a blue colorant is locally injected, endermically or by use of an endoscope, into the vicinity surrounding the diseased area directly preceding the performance of cancer removal surgery. The injected blue colorant advances from the position at which it was injected toward the lymph nodes, and reaches the sentinel lymph node 5-15 minutes after injection.
The examiner visually detects the sentinel lymph node, which has been dyed blue. However, lymph nodes are often covered with fatty tissue, etc., and the sentinel lymph node must be searched for while such tissue is peeled away, which makes for a time consuming detection process. Moreover, while such searching and peeling away of tissues obstructing view of the sentinel lymph node is being performed, there are incidences in which the blue colorant advances beyond the sentinel lymph node and reaches other lymph nodes, whereby a problem arises in that it becomes difficult to detect the sentinel lymph node.
In addition, a method employing radioisotopes an, RI method, has also been developed. According to the Ri method, a radioisotope is locally injected, endermically or by use of an endoscope, on the day prior to surgery into the vicinity surrounding the diseased area. The injected radioisotope advances from the position at which it was injected towards the lymph nodes and stays for a set duration at the sentinel lymph node. A few hours after the radioisotope is injected a lymphosynthography is performed, and the approximate position is marked. When the surgery to remove the cancer is performed, the marked position is cut open, and employing a cancer gamma-probe, the gamma radiation emitted by the lymph nodes in the vicinity of the opened position is detected; the lymph node emitting the most gamma radiation is detected as the sentinel lymph node. According to the RI method, because the tracer reaches the lymph nodes beyond the sentinel lymph node in a short time and detection of the sentinel lymph node does not become difficult, and the sentinel lymph node can be detected even though it is covered with fatty, etc. tissue, although the detection rate is improved, because radiation is employed, management of the surgical procedure is complicated, and because a gamma probe is used, problems arise in that the detection process must be performed point-by-point and the information obtained cannot be made into an image, and the procedure is expensive.
On the other hand, in recent years a method employing fluorescent colorants, the fluorescent colorant method, for detecting diseased tissue has been proposed; a method as disclosed in PCT International Publication No. WO98/48845 for example, wherein a cyanine colorant is thrown onto a living tissue, and by irradiation thereof by stimulating light, the diseased tissue is detected.
According to the fluorescent colorant method disclosed in aforementioned WO98/48845, a photosensitive material that emits fluorescent light upon stimulation thereof by a stimulating light is applied in advance as a fluorescent diagnostic agent to the tissue that is the subject of an examination. Stimulating light in the wavelength band to which the fluorescent diagnostic agent is sensitive is irradiated onto the diseased tissue, causing fluorescent light to be emitted from the fluorescent diagnostic agent accumulated thereon, and the area into which the fluorescent diagnostic agent has permeated, which contains the diseased tissue, is detected by reception of this fluorescent light. In addition, it is indicated that the fluorescent diagnostic agent is also accumulated on the sentinel lymph node, and that detection thereof is possible.
However, in aforementioned PCT International Publication No. WO98/48845, there is no mention of a definite sentinel lymph node detection method or system. Further, regardless of the fact that the fluorescent colorant method disclosed therein suffers the same difficulty in detecting the sentinel lymph node due to the covering thereof by fatty, etc. tissues, as in the normal detection method, there is a problem in that no consideration is addressed therein to this difficulty.
The present invention has been developed in consideration of the circumstances described above, and it is a primary objective of the present invention to provide a sentinel lymph node detection method and system therefor capable of accurately and easily detecting the sentinel lymph node by use of a fluorescent colorant.
According to the first sentinel lymph node detection system of the present invention, the fluorescent light, which is close to the near-infrared wavelength band, emitted from the near-infrared fluorescent colorant that has been injected into the area of tissue under examination in the vicinity of the diseased portion, which contains the sentinel lymph node, upon irradiation thereof by stimulating light, is focused as a near-infrared fluorescent image, and the near-infrared fluorescent image is converted to a visible image.
In addition, a method can also be adopted wherein a normal image composed of the reflected light reflected by the area of tissue under examination that has been irradiated by an illuminating light, which is composed of visible light, can be superposed with the visible image that has been converted from the near-fluorescent image, and observed.
Further, a method wherein the normal image can be superposed with aforementioned visible image and focused, and the focused image observed, as a visible image, is also preferable.
According to the second sentinel lymph node detection system of the present invention, the fluorescent light, which is close to the near-infrared wavelength band, emitted from near-infrared fluorescent colorant that has been injected into the area of tissue under examination in the vicinity of the diseased portion, which includes the sentinel lymph node, upon irradiation thereof by stimulating light, is photographed by a fluorescent image photographing means, and based on the photographed near-infrared fluorescent image, a visible image is formed, and the visible image displayed.
In addition, a method can also be adopted wherein a normal image of the reflected light reflected by the area of tissue under examination that has been irradiated by an illuminating light is photographed as a normal image, said normal image is made into a normal image and superposed with the visible image, and the superposed image displayed.
It is preferable that the normal image be photographed as a color mage.
In addition, the first sentinel lymph node detection system according to the present invention comprises a stimulating light projecting means for projecting stimulating light, which has a wavelength in the wavelength range of light that stimulates the near-infrared fluorescent colorant, onto the area of tissue under examination in the vicinity of the diseased portion, which includes the sentinel lymph node and into which said near-infrared fluorescent colorant for emitting fluorescent light having a wavelength band within the near-infrared wavelength band has been injected in advance, a fluorescent light image focusing means for focusing the fluorescent light having a wavelength band within the near-infrared wavelength band emitted from the near-infrared fluorescent colorant injected into the area of tissue under examination, and a visible-image converting means for converting the fluorescent image having a wavelength band within the near-infrared wavelength band focused by the fluorescent light image focusing means to a visible image composed of light having a wavelength band within the visible spectrum.
Here, xe2x80x9cthe near-infrared wavelength bandxe2x80x9d refers to the 700 nm to 1500 nm band of frequencies.
In addition, xe2x80x9cconverting meansxe2x80x9d refers to a means for converting a near-infrared fluorescent image to a visible image; for example, an IR converter, IR viewer, etc. that converts near-infrared light input thereto to visible light and outputs said visible light.
Further, the first sentinel lymph node detection system according to the present invention may also be provided with an illuminating-light projecting means for projecting illuminating light composed of visible light onto the area of tissue under examination, and an observation means for observing the normal image composed of the illuminating light reflected by the area of tissue under examination image superposed with the visible image, which has been converted from the near-infrared image.
Still further, it is preferable that the first sentinel lymph node detection system according to the present invention also have a focusing means for superposing said normal image with said visible image, and focusing the superposed image, and an observation means for observing the image focused by the focusing means and the visible image.
The second sentinel lymph node detection system according to the present invention comprises a stimulating light projecting means for projecting stimulating light, which has a wavelength in the wavelength range of light that stimulates the near-infrared fluorescent colorant, onto the area of tissue under examination in the vicinity of the diseased portion, which includes the sentinel lymph node and into which said near-infrared fluorescent colorant for emitting fluorescent light having a wavelength band within the near-infrared wavelength band has been injected in advance, a fluorescent image photographing means for photographing the fluorescent light having a wavelength band within the near-infrared wavelength band emitted from the near-infrared fluorescent colorant injected into the area of tissue under examination, a fluorescent image forming means for forming a visible image based on the fluorescent image having a wavelength band within the near-infrared wavelength band photographed by said fluorescent image photographing means, and a display means for displaying said visible image.
In addition, the second sentinel lymph node detection system according to the present invention comprises an illuminating light projecting means for projecting illuminating light composed of visible light onto the area of tissue under examination, a normal image photographing means for photographing the normal image composed of the reflected light reflected by the area of tissue under examination upon illumination thereof by the illuminating light, a normal-image forming means for forming a normal image from the photographed signal photographed by the normal image photographing means, and a superposed image forming means for forming a superposed image of the superposed visible image and normal image, wherein the display means can be a means for displaying superposed images.
It is preferable that a color image photographing means be utilized as aforementioned normal image photographing means. It is preferable that the fluorescent light image focusing means, the converting means and the observation means, or the fluorescent image photographing means, the fluorescent image forming means, the normal image photographing means, the normal-image forming means, the superposed image forming means and the display means are constructed in the form of a pair of goggles, a laparoscope, or a microscope.
It is preferable that the wavelength band of aforementioned stimulating light be a wavelength and of 700 nm or larger.
In this case, in order to improve the stimulating light absorption rate of the near-infrared fluorescent colorant, it is desirable that light having a wavelength band near the peak frequency of the spectra of light that can be absorbed by the near-infrared fluorescent colorant be utilized as the stimulating light.
Further, when the near-infrared fluorescent colorant is irradiated by stimulating light, it is preferable that the largest wavelength of light absorbed by the near-infrared fluorescent colorant be 700 nm or larger.
It is optimal that a cyanine colorant, of which the largest absorbable wavelength is within the near-infrared wavelength band, be utilized as the near-infrared fluorescent colorant; in particular, it is preferable that indocyanine green be utilized.
Normally, there are many occurrences in which sentinel lymph nodes are covered in fatty, etc. tissues, when sentinel lymph node detection employing the fluorescent colorant method is performed, due to the fatty, etc. a great deal of stimulating light and fluorescent light are absorbed by the tissue covering the sentinel lymph node, and there is a fear that accuracy in detecting the sentinel lymph node becomes reduced, or that detection of the sentinel lymph node becomes impossible.
FIG. 1 shows the degree of absorption for hemoglobin, etc. contained in living tissue; it is known that wavelengths of light in the visible spectra are easily absorbed by living tissue, and that wavelengths above approximately 700 nm are difficult for living tissue to absorb. Because of this, if the wavelengths of both the stimulating and the fluorescent light are near the near-infrared wavelength band (700 nm-1500 nm), it is difficult for the stimulating light and the fluorescent light to be affected by the fatty, etc. tissue covering a sentinel lymph node.
In addition, because autofluorescence does not occur in living tissue due to exposure thereof to near-infrared wavelengths of light, this can contribute to improving the S/N ratio during observation.
According to the first sentinel lymph node detection system described above, a near-infrared fluorescent colorant is locally injected in advance into the vicinity of diseased tissue, and light having a wavelength band in the near-infrared wavelength range is projected as stimulating light onto the area within the part of the vicinity into which the near-infrared fluorescent colorant has been injected where the sentinel lymph node is presumed to be. Because the stimulating light is in the near-infrared wavelength band, even if the sentinel lymph node is covered by fatty, etc. tissue, it is easy for the stimulating light to reach the sentinel lymph node. In addition, because the near-infrared fluorescent colorant for emitting near-infrared fluorescent light has been accumulated on the sentinel lymph node in advance, because it is also easy for the fluorescent light emitted from the sentinel lymph node to reach the surface of the tissue, by converting the near-infrared fluorescent image emitted from the area of the tissue under examination into a visible image and displaying said visible image, the sentinel lymph node can be detected easily and with a high degree of accuracy.
In addition, by providing an observation means for superposing a normal image, which is formed of light reflected by the area of tissue under examination upon illumination thereof by illuminating light in the visible spectra, with a visible image, and observing this superposed image and the visible image, the examiner can observe both said visible and said normal image at the same time, and can easily confirm the position of the sentinel lymph node contained within the area of the tissue under examination.
Further, if aforementioned observation means is also provided with an image focusing means for superposing the normal image with the visible image and focusing the superposed image, and an observation optical means for observing this superposed image and the visible image, because the positions of the normal image and the visible image are substantially matched, the visual verifiability when the normal image and the visible image are observed at the same time is improved.
According to the first sentinel lymph node detection system: a near-infrared fluorescent colorant is locally injected in advance into the vicinity of diseased tissue; light having a wavelength band in the near-infrared wavelength range is projected as stimulating light onto the area within the part of the vicinity into which the near-infrared fluorescent colorant has been injected where the sentinel lymph node is presumed to be; the near-infrared fluorescent light emitted from the area of the tissue under examination is photographed by a fluorescent image photographing means, and by displaying said photographed image as a visible image, even for cases in which the sentinel image is covered by fatty, etc. tissue, it is easy for the stimulating light to reach the sentinel lymph node, and because it is also easy for the fluorescent light emitted from the near-infrared fluorescent colorant accumulated on the sentinel lymph node to reach the surface of the tissue, the sentinel lymph node is easily displayed as a visual image, and thereby, the sentinel image can be easily detected with a high degree of accuracy.
In addition, because the fluorescent light emitted from the sentinel lymph node can be rendered as a visible image, it is possible to halt or record a displayed image, and the ease with which the sentinel lymph node is detected is improved one level.
Further, by displaying a superposed image formed of the normal image composed of reflected illuminating light superposed with the fluorescent image, the examiner can observe the fluorescent image and the normal image at the same time, and the position of the sentinel lymph node contained within the area of tissue under examination can be easily confirmed.
If the normal image is photographed as a color image, the relative relation of the actual position of the area of tissue under examination to that of the displayed position thereof can be confirmed, and identification of the sentinel lymph node becomes easy.
If the sentinel lymph node detection system described above is constructed in the form of a pair of goggles, when performing detection of the sentinel lymph node, the examiner can freely use both hands, and ease of operability of the system is thereby improved.
Further, if the sentinel lymph detecting system is constructed in the form of a laparoscope, when performing detection of the sentinel lymph node, there is no need to carryout an abdominal operation and the burden on the patient is thereby reduced.
Still further, if the sentinel lymph node detection system described above is constructed in the form of a microscope, when performing detection of the sentinel lymph node, the detailed position of the sentinel lymph node can be confirmed, whereby the fear of inflicting damage to the surrounding tissues of the sentinel lymph node during performance of the surgical procedure to remove the sentinel lymph node is reduced, and the burden on the patient is reduced.
If the wavelength of the stimulating light is 700 nm or larger, it is difficult for it to be absorbed by the tissue. In addition, if the largest wavelength absorbable by the near-infrared fluorescent colorant is 700 nm or larger, the stimulating light is efficiently absorbed by the near-infrared fluorescent colorant.
As described above, if a cyanine colorant, of which the largest absorbable wavelength is near the near-infrared wavelength band, is utilized as the near-infrared fluorescent colorant, when said near-infrared fluorescent colorant is irradiated by stimulating light having a wavelength band in the near-infrared range, fluorescent light is efficiently emitted therefrom. In particular, if Indocyanine green is utilized, not only is absorption by the tissue not affected by dispersion, but because there is no adverse effect due to background autofluorescence, when focusing and photographing the fluorescent light emitted by the sentinel lymph node, only the fluorescent light that is the object of said focusing and photographing can be easily focused and photographed, and the reliability of the system can be improved.